CA2521202A1 - Pyrazoles substitues en position 1,3 et 4 utilises en tant qu'antagonistes des recepteurs 5-ht pour le traitement de psychoses et de troubles neurologiques - Google Patents

Pyrazoles substitues en position 1,3 et 4 utilises en tant qu'antagonistes des recepteurs 5-ht pour le traitement de psychoses et de troubles neurologiques Download PDF

Info

Publication number: CA2521202A1
Authority: CA; Canada
Prior art keywords: formula; compounds; denotes; solvates; salts
Prior art date: 2003-04-05
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002521202A

Other languages

English (en)

Inventor

Kai Schiemann

Oliver Schadt

Christoph Van Amsterdam

Gerd Bartoszyk

Christoph Seyfried

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Merck Patent GmbH

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2003-04-05

Filing date

2004-03-08

Publication date

2004-10-21

2004-03-08 Application filed by Individual filed Critical Individual

2004-10-21 Publication of CA2521202A1 publication Critical patent/CA2521202A1/fr

Status Abandoned legal-status Critical Current

Links

238000011282 treatment Methods 0.000 title claims description 22
208000028017 Psychotic disease Diseases 0.000 title claims description 4
208000012902 Nervous system disease Diseases 0.000 title claims description 3
208000025966 Neurological disease Diseases 0.000 title claims description 3
229940127239 5 Hydroxytryptamine receptor antagonist Drugs 0.000 title 1
150000003217 pyrazoles Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 81
150000003839 salts Chemical class 0.000 claims abstract description 36
239000012453 solvate Substances 0.000 claims abstract description 26
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 claims abstract description 5
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 claims abstract description 5
-1 ethyl- Chemical group 0.000 claims description 46
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 34
239000003814 drug Substances 0.000 claims description 21
238000002360 preparation method Methods 0.000 claims description 15
125000004432 carbon atom Chemical group C* 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 11
239000000203 mixture Substances 0.000 claims description 11
238000000034 method Methods 0.000 claims description 9
238000011321 prophylaxis Methods 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 6
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 6
230000009471 action Effects 0.000 claims description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 5
201000010099 disease Diseases 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000005842 heteroatom Chemical group 0.000 claims description 4
239000007788 liquid Substances 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
239000007787 solid Substances 0.000 claims description 4
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 3
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
208000000103 Anorexia Nervosa Diseases 0.000 claims description 3
208000032841 Bulimia Diseases 0.000 claims description 3
206010006550 Bulimia nervosa Diseases 0.000 claims description 3
208000030814 Eating disease Diseases 0.000 claims description 3
208000019454 Feeding and Eating disease Diseases 0.000 claims description 3
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 3
239000002671 adjuvant Substances 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
235000014632 disordered eating Nutrition 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
229920006395 saturated elastomer Polymers 0.000 claims description 3
125000004361 3,4,5-trifluorophenyl group Chemical group [H]C1=C(F)C(F)=C(F)C([H])=C1* 0.000 claims description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 claims description 2
101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 claims description 2
206010036618 Premenstrual syndrome Diseases 0.000 claims description 2
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
150000007514 bases Chemical class 0.000 claims description 2
239000002552 dosage form Substances 0.000 claims description 2
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims 1
CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims 1
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
239000003446 ligand Substances 0.000 abstract description 4
235000013350 formula milk Nutrition 0.000 description 53
239000004480 active ingredient Substances 0.000 description 20
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
239000000243 solution Substances 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
150000003254 radicals Chemical class 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 7
239000003826 tablet Substances 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
102000005962 receptors Human genes 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
239000000126 substance Substances 0.000 description 6
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
239000002775 capsule Substances 0.000 description 4
238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
YKZURXNDHGYIOB-UHFFFAOYSA-N 1-[[1-[4-(1,3-benzodioxol-5-yl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]-4-methylpiperazine Chemical compound C1CN(C)CCN1CC1=CN(C=2C=CC(=CC=2)C=2C=C3OCOC3=CC=2)N=C1C1=CC=CO1 YKZURXNDHGYIOB-UHFFFAOYSA-N 0.000 description 3
102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
208000024827 Alzheimer disease Diseases 0.000 description 3
208000019901 Anxiety disease Diseases 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
101150104779 HTR2A gene Proteins 0.000 description 3
208000002193 Pain Diseases 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
210000003169 central nervous system Anatomy 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000000875 corresponding effect Effects 0.000 description 3
230000000694 effects Effects 0.000 description 3
235000019439 ethyl acetate Nutrition 0.000 description 3
229940093499 ethyl acetate Drugs 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
238000010992 reflux Methods 0.000 description 3
201000000980 schizophrenia Diseases 0.000 description 3
239000007921 spray Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000000829 suppository Substances 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
ZMMRIONHZXULFC-UHFFFAOYSA-N 1-[3-(2-fluorophenyl)-1-phenylpyrazol-4-yl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CN(C=2C=CC=CC=2)N=C1C1=CC=CC=C1F ZMMRIONHZXULFC-UHFFFAOYSA-N 0.000 description 2
BUPQBGPSLXNELO-UHFFFAOYSA-N 1-[[1-(4-bromophenyl)-3-(furan-2-yl)pyrazol-4-yl]methyl]-4-methylpiperazine Chemical compound C1CN(C)CCN1CC1=CN(C=2C=CC(Br)=CC=2)N=C1C1=CC=CO1 BUPQBGPSLXNELO-UHFFFAOYSA-N 0.000 description 2
ZXJKSGUUIPLQCB-UHFFFAOYSA-N 1-[[1-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]-4-methyl-1,4-diazepane Chemical compound C1CN(C)CCCN1CC1=CN(C=2C=CC(=CC=2)C=2C=C3OCCOC3=CC=2)N=C1C1=CC=CO1 ZXJKSGUUIPLQCB-UHFFFAOYSA-N 0.000 description 2
XUYBYXWSTRQCQL-UHFFFAOYSA-N 1-[[1-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]piperazine Chemical compound C=1N(C=2C=CC(=CC=2)C=2C=C3OCCOC3=CC=2)N=C(C=2OC=CC=2)C=1CN1CCNCC1 XUYBYXWSTRQCQL-UHFFFAOYSA-N 0.000 description 2
KZSJJCBGVOCUOL-UHFFFAOYSA-N 1-[[1-[4-(3-fluorophenyl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]piperazine Chemical compound FC1=CC=CC(C=2C=CC(=CC=2)N2N=C(C(CN3CCNCC3)=C2)C=2OC=CC=2)=C1 KZSJJCBGVOCUOL-UHFFFAOYSA-N 0.000 description 2
MAQCZOUFJUZUQJ-UHFFFAOYSA-N 1-[[1-[4-(4-fluorophenyl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]piperazine Chemical compound C1=CC(F)=CC=C1C1=CC=C(N2N=C(C(CN3CCNCC3)=C2)C=2OC=CC=2)C=C1 MAQCZOUFJUZUQJ-UHFFFAOYSA-N 0.000 description 2
RRWCULUAWKAUNJ-UHFFFAOYSA-N 1-[[3-(2-fluorophenyl)-1-(4-phenylphenyl)pyrazol-4-yl]methyl]-4-methylpiperazine Chemical compound C1CN(C)CCN1CC1=CN(C=2C=CC(=CC=2)C=2C=CC=CC=2)N=C1C1=CC=CC=C1F RRWCULUAWKAUNJ-UHFFFAOYSA-N 0.000 description 2
VDOYKSHUYHYAGH-UHFFFAOYSA-N 1-[[3-(2-fluorophenyl)-1-phenylpyrazol-4-yl]methyl]-4-methylpiperazine Chemical compound C1CN(C)CCN1CC1=CN(C=2C=CC=CC=2)N=C1C1=CC=CC=C1F VDOYKSHUYHYAGH-UHFFFAOYSA-N 0.000 description 2
AKUNVPXOSPUULI-UHFFFAOYSA-N 1-[[3-(2-fluorophenyl)-1-phenylpyrazol-4-yl]methyl]pyrrolidin-3-ol Chemical compound C1C(O)CCN1CC1=CN(C=2C=CC=CC=2)N=C1C1=CC=CC=C1F AKUNVPXOSPUULI-UHFFFAOYSA-N 0.000 description 2
YNTCHOAGPQZFHN-UHFFFAOYSA-N 1-[[3-(furan-2-yl)-1-[4-(4-methoxyphenyl)phenyl]pyrazol-4-yl]methyl]piperazine Chemical compound C1=CC(OC)=CC=C1C1=CC=C(N2N=C(C(CN3CCNCC3)=C2)C=2OC=CC=2)C=C1 YNTCHOAGPQZFHN-UHFFFAOYSA-N 0.000 description 2
VYPZFNXDGKXNEY-UHFFFAOYSA-N 1-cyclopentyl-4-[[1-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]piperazine Chemical compound C=1N(C=2C=CC(=CC=2)C=2C=C3OCCOC3=CC=2)N=C(C=2OC=CC=2)C=1CN(CC1)CCN1C1CCCC1 VYPZFNXDGKXNEY-UHFFFAOYSA-N 0.000 description 2
XULYYONTXLEIKQ-UHFFFAOYSA-N 1-ethyl-4-[[3-(2-fluorophenyl)-1-phenylpyrazol-4-yl]methyl]piperazine Chemical compound C1CN(CC)CCN1CC1=CN(C=2C=CC=CC=2)N=C1C1=CC=CC=C1F XULYYONTXLEIKQ-UHFFFAOYSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
XQYRGMQMMUUKQK-UHFFFAOYSA-N 4-[[1-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]morpholine Chemical compound C=1N(C=2C=CC(=CC=2)C=2C=C3OCCOC3=CC=2)N=C(C=2OC=CC=2)C=1CN1CCOCC1 XQYRGMQMMUUKQK-UHFFFAOYSA-N 0.000 description 2
HIMFMDYOIQJVLY-UHFFFAOYSA-N 4-[[1-[4-(3-fluorophenyl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]morpholine Chemical compound FC1=CC=CC(C=2C=CC(=CC=2)N2N=C(C(CN3CCOCC3)=C2)C=2OC=CC=2)=C1 HIMFMDYOIQJVLY-UHFFFAOYSA-N 0.000 description 2
WKRUYGDKRQINGO-UHFFFAOYSA-N 4-[[1-[4-(4-fluorophenyl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]morpholine Chemical compound C1=CC(F)=CC=C1C1=CC=C(N2N=C(C(CN3CCOCC3)=C2)C=2OC=CC=2)C=C1 WKRUYGDKRQINGO-UHFFFAOYSA-N 0.000 description 2
PLXPMFKRYZOQNC-UHFFFAOYSA-N 4-[[3-(2-fluorophenyl)-1-phenylpyrazol-4-yl]methyl]morpholine Chemical compound FC1=CC=CC=C1C1=NN(C=2C=CC=CC=2)C=C1CN1CCOCC1 PLXPMFKRYZOQNC-UHFFFAOYSA-N 0.000 description 2
NRDYWJMWBGNNIQ-UHFFFAOYSA-N 4-[[3-(furan-2-yl)-1-[4-(4-methoxyphenyl)phenyl]pyrazol-4-yl]methyl]morpholine Chemical compound C1=CC(OC)=CC=C1C1=CC=C(N2N=C(C(CN3CCOCC3)=C2)C=2OC=CC=2)C=C1 NRDYWJMWBGNNIQ-UHFFFAOYSA-N 0.000 description 2
DLQXGJRPZSYHRC-UHFFFAOYSA-N 4-[[3-(furan-2-yl)-1-phenylpyrazol-4-yl]methyl]morpholine Chemical compound C=1N(C=2C=CC=CC=2)N=C(C=2OC=CC=2)C=1CN1CCOCC1 DLQXGJRPZSYHRC-UHFFFAOYSA-N 0.000 description 2
RJWLLQWLBMJCFD-UHFFFAOYSA-N 4-methylpiperazin-1-amine Chemical compound CN1CCN(N)CC1 RJWLLQWLBMJCFD-UHFFFAOYSA-N 0.000 description 2
102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
208000020706 Autistic disease Diseases 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
206010012289 Dementia Diseases 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
239000001828 Gelatine Substances 0.000 description 2
102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 description 2
108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
208000019695 Migraine disease Diseases 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
208000018737 Parkinson disease Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
210000001367 artery Anatomy 0.000 description 2
230000037396 body weight Effects 0.000 description 2
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
238000001816 cooling Methods 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
238000001514 detection method Methods 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000006196 drop Substances 0.000 description 2
239000000975 dye Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
206010027599 migraine Diseases 0.000 description 2
229940113083 morpholine Drugs 0.000 description 2
WIXOVUYYGPMCMW-UHFFFAOYSA-N n-[[1-[4-(4-fluorophenyl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]-n,1-dimethylpyrrolidin-3-amine Chemical compound C1CN(C)CC1N(C)CC1=CN(C=2C=CC(=CC=2)C=2C=CC(F)=CC=2)N=C1C1=CC=CO1 WIXOVUYYGPMCMW-UHFFFAOYSA-N 0.000 description 2
PGWYXKPOAOTMSG-UHFFFAOYSA-N n-[[3-(2-fluorophenyl)-1-phenylpyrazol-4-yl]methyl]-n,1-dimethylpyrrolidin-3-amine Chemical compound C1CN(C)CC1N(C)CC1=CN(C=2C=CC=CC=2)N=C1C1=CC=CC=C1F PGWYXKPOAOTMSG-UHFFFAOYSA-N 0.000 description 2
UUWAAPUZLRTTOD-UHFFFAOYSA-N n-[[3-(2-fluorophenyl)-1-phenylpyrazol-4-yl]methyl]-n-methylethanamine Chemical compound CCN(C)CC1=CN(C=2C=CC=CC=2)N=C1C1=CC=CC=C1F UUWAAPUZLRTTOD-UHFFFAOYSA-N 0.000 description 2
FPDODTAJSUPMBU-UHFFFAOYSA-N n-[[3-(furan-2-yl)-1-[4-(4-methoxyphenyl)phenyl]pyrazol-4-yl]methyl]-n,1-dimethylpyrrolidin-3-amine Chemical compound C1=CC(OC)=CC=C1C1=CC=C(N2N=C(C(CN(C)C3CN(C)CC3)=C2)C=2OC=CC=2)C=C1 FPDODTAJSUPMBU-UHFFFAOYSA-N 0.000 description 2
FRZTYHREBGTCGA-UHFFFAOYSA-N n-[[3-(furan-2-yl)-1-phenylpyrazol-4-yl]methyl]-n,1-dimethylpyrrolidin-3-amine Chemical compound C1CN(C)CC1N(C)CC1=CN(C=2C=CC=CC=2)N=C1C1=CC=CO1 FRZTYHREBGTCGA-UHFFFAOYSA-N 0.000 description 2
HOHJRLOVTBYOAW-UHFFFAOYSA-N n-ethyl-n-[[1-[4-(3-fluorophenyl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]ethanamine Chemical compound CCN(CC)CC1=CN(C=2C=CC(=CC=2)C=2C=C(F)C=CC=2)N=C1C1=CC=CO1 HOHJRLOVTBYOAW-UHFFFAOYSA-N 0.000 description 2
DLZAMECITYTNFO-UHFFFAOYSA-N n-ethyl-n-[[1-[4-(4-fluorophenyl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]ethanamine Chemical compound CCN(CC)CC1=CN(C=2C=CC(=CC=2)C=2C=CC(F)=CC=2)N=C1C1=CC=CO1 DLZAMECITYTNFO-UHFFFAOYSA-N 0.000 description 2
XYOGNRCTJBOKRX-UHFFFAOYSA-N n-ethyl-n-[[3-(furan-2-yl)-1-[4-(4-methoxyphenyl)phenyl]pyrazol-4-yl]methyl]ethanamine Chemical compound CCN(CC)CC1=CN(C=2C=CC(=CC=2)C=2C=CC(OC)=CC=2)N=C1C1=CC=CO1 XYOGNRCTJBOKRX-UHFFFAOYSA-N 0.000 description 2
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
239000011664 nicotinic acid Substances 0.000 description 2
235000001968 nicotinic acid Nutrition 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
239000002674 ointment Substances 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
235000011007 phosphoric acid Nutrition 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
229920001592 potato starch Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
MAVITAALDQIMHQ-UHFFFAOYSA-N tert-butyl 4-[[1-[4-(4-fluorophenyl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=CN(C=2C=CC(=CC=2)C=2C=CC(F)=CC=2)N=C1C1=CC=CO1 MAVITAALDQIMHQ-UHFFFAOYSA-N 0.000 description 2
IVJVENZNULWTLS-UHFFFAOYSA-N tert-butyl 4-[[3-(furan-2-yl)-1-[4-(4-methoxyphenyl)phenyl]pyrazol-4-yl]methyl]piperazine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1C1=CC=C(N2N=C(C(CN3CCN(CC3)C(=O)OC(C)(C)C)=C2)C=2OC=CC=2)C=C1 IVJVENZNULWTLS-UHFFFAOYSA-N 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
229940099259 vaseline Drugs 0.000 description 2
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
PTSWEKLDFVDAKU-UHFFFAOYSA-N 1-[[3-(furan-2-yl)-1-phenylpyrazol-4-yl]methyl]piperazine Chemical compound C=1N(C=2C=CC=CC=2)N=C(C=2OC=CC=2)C=1CN1CCNCC1 PTSWEKLDFVDAKU-UHFFFAOYSA-N 0.000 description 1
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical group COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
KLLLJCACIRKBDT-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical class N1C2=CC=CC=C2C=C1C1=CC=CC=C1 KLLLJCACIRKBDT-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
MSKYBZXLUDJNOV-UHFFFAOYSA-N 4-[[1-[4-(3-fluorophenyl)phenyl]-3-(furan-2-yl)pyrazol-4-yl]methyl]piperazine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCN1CC1=CN(C=2C=CC(=CC=2)C=2C=C(F)C=CC=2)N=C1C1=CC=CO1 MSKYBZXLUDJNOV-UHFFFAOYSA-N 0.000 description 1
LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
125000006043 5-hexenyl group Chemical group 0.000 description 1
208000008811 Agoraphobia Diseases 0.000 description 1
206010001540 Akathisia Diseases 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
208000036640 Asperger disease Diseases 0.000 description 1
201000006062 Asperger syndrome Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
206010003805 Autism Diseases 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
208000028698 Cognitive impairment Diseases 0.000 description 1
208000003890 Coronary Vasospasm Diseases 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
208000012239 Developmental disease Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
208000012661 Dyskinesia Diseases 0.000 description 1
BGHDUTQZGWOQIA-VQSKNWBGSA-N Ergovaline Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)C(C)C)C)C2)=C3C2=CNC3=C1 BGHDUTQZGWOQIA-VQSKNWBGSA-N 0.000 description 1
208000027776 Extrapyramidal disease Diseases 0.000 description 1
208000001640 Fibromyalgia Diseases 0.000 description 1
208000018522 Gastrointestinal disease Diseases 0.000 description 1
208000010412 Glaucoma Diseases 0.000 description 1
101150013372 Htr2c gene Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
208000008454 Hyperhidrosis Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
208000020358 Learning disease Diseases 0.000 description 1
208000026139 Memory disease Diseases 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
206010057852 Nicotine dependence Diseases 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
206010029897 Obsessive thoughts Diseases 0.000 description 1
206010033664 Panic attack Diseases 0.000 description 1
208000005374 Poisoning Diseases 0.000 description 1
208000006289 Rett Syndrome Diseases 0.000 description 1
201000001880 Sexual dysfunction Diseases 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
208000001871 Tachycardia Diseases 0.000 description 1
206010043118 Tardive Dyskinesia Diseases 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
208000025569 Tobacco Use disease Diseases 0.000 description 1
208000000323 Tourette Syndrome Diseases 0.000 description 1
208000016620 Tourette disease Diseases 0.000 description 1
206010044565 Tremor Diseases 0.000 description 1
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
206010047139 Vasoconstriction Diseases 0.000 description 1
206010047163 Vasospasm Diseases 0.000 description 1
238000007239 Wittig reaction Methods 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
125000002723 alicyclic group Chemical group 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
239000003708 ampul Substances 0.000 description 1
208000022531 anorexia Diseases 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
239000000164 antipsychotic agent Substances 0.000 description 1
229940005529 antipsychotics Drugs 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
239000002249 anxiolytic agent Substances 0.000 description 1
230000000949 anxiolytic effect Effects 0.000 description 1
229940005530 anxiolytics Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000006399 behavior Effects 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
150000003938 benzyl alcohols Chemical class 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
229950005499 carbon tetrachloride Drugs 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
210000000748 cardiovascular system Anatomy 0.000 description 1
229940116592 central nervous system diagnostic radiopharmaceuticals Drugs 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
229960001701 chloroform Drugs 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229960003920 cocaine Drugs 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
208000010877 cognitive disease Diseases 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
206010061428 decreased appetite Diseases 0.000 description 1
230000006735 deficit Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
150000004683 dihydrates Chemical class 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000002651 drug therapy Methods 0.000 description 1
208000010118 dystonia Diseases 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
208000030172 endocrine system disease Diseases 0.000 description 1
150000002084 enol ethers Chemical class 0.000 description 1
BGHDUTQZGWOQIA-RKUMIMICSA-N ergovaline Natural products O=C(N[C@@]1(C)C(=O)N2[C@H](C(C)C)C(=O)N3[C@@H]([C@]2(O)O1)CCC3)[C@@H]1C=C2[C@H](N(C)C1)Cc1c3c([nH]c1)cccc23 BGHDUTQZGWOQIA-RKUMIMICSA-N 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000029142 excretion Effects 0.000 description 1
239000003889 eye drop Substances 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
235000011389 fruit/vegetable juice Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
235000013773 glyceryl triacetate Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
230000036541 health Effects 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
208000013403 hyperactivity Diseases 0.000 description 1
208000031424 hyperprolactinemia Diseases 0.000 description 1
125000002632 imidazolidinyl group Chemical group 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
208000014674 injury Diseases 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
230000004410 intraocular pressure Effects 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
201000003723 learning disability Diseases 0.000 description 1
210000004558 lewy body Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
206010027175 memory impairment Diseases 0.000 description 1
230000003340 mental effect Effects 0.000 description 1
SDMCZCALYDCRBH-UHFFFAOYSA-N methoxymethyl(triphenyl)phosphanium Chemical class C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SDMCZCALYDCRBH-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
208000004296 neuralgia Diseases 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
230000000701 neuroleptic effect Effects 0.000 description 1
229960002715 nicotine Drugs 0.000 description 1
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
229960003512 nicotinic acid Drugs 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002826 nitrites Chemical class 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
229940127240 opiate Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
208000019906 panic disease Diseases 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
231100000572 poisoning Toxicity 0.000 description 1
230000000607 poisoning effect Effects 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000011118 potassium hydroxide Nutrition 0.000 description 1
229940093932 potassium hydroxide Drugs 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
239000000047 product Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000003368 psychostimulant agent Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
230000004044 response Effects 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
231100000872 sexual dysfunction Toxicity 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
201000002859 sleep apnea Diseases 0.000 description 1
208000019116 sleep disease Diseases 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000008347 soybean phospholipid Substances 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000035900 sweating Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000006794 tachycardia Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000008733 trauma Effects 0.000 description 1
229960002622 triacetin Drugs 0.000 description 1
UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
230000025033 vasoconstriction Effects 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Heart & Thoracic Surgery (AREA)
Psychiatry (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Obesity (AREA)
Psychology (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Hematology (AREA)
Diabetes (AREA)
Addiction (AREA)
Reproductive Health (AREA)
Gynecology & Obstetrics (AREA)
Rheumatology (AREA)
Hospice & Palliative Care (AREA)
Vascular Medicine (AREA)
Pregnancy & Childbirth (AREA)
Child & Adolescent Psychology (AREA)
Endocrinology (AREA)
Nutrition Science (AREA)
Pulmonology (AREA)
Toxicology (AREA)

CA002521202A 2003-04-05 2004-03-08 Pyrazoles substitues en position 1,3 et 4 utilises en tant qu'antagonistes des recepteurs 5-ht pour le traitement de psychoses et de troubles neurologiques Abandoned CA2521202A1 (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE10315573.2		2003-04-05
DE2003115573 DE10315573A1 (de)	2003-04-05	2003-04-05	Substituierte Pyrazole
PCT/EP2004/002354 WO2004089910A1 (fr)	2003-04-05	2004-03-08	Pyrazoles substitues en position 1,3 et 4 utilises en tant qu'antagonistes des recepteurs 5-ht pour le traitement de psychoses et de troubles neurologiques

Publications (1)

Publication Number	Publication Date
CA2521202A1 true CA2521202A1 (fr)	2004-10-21

Family

ID=32981074

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002521202A Abandoned CA2521202A1 (fr)	2003-04-05	2004-03-08	Pyrazoles substitues en position 1,3 et 4 utilises en tant qu'antagonistes des recepteurs 5-ht pour le traitement de psychoses et de troubles neurologiques

Country Status (16)

Country	Link
US (1)	US7566709B2 (fr)
EP (1)	EP1611107B1 (fr)
JP (1)	JP4740116B2 (fr)
KR (1)	KR20050119194A (fr)
CN (1)	CN1768043A (fr)
AR (1)	AR043838A1 (fr)
AT (1)	ATE478052T1 (fr)
AU (1)	AU2004228121B2 (fr)
BR (1)	BRPI0409002A (fr)
CA (1)	CA2521202A1 (fr)
DE (2)	DE10315573A1 (fr)
ES (1)	ES2349922T3 (fr)
MX (1)	MXPA05010646A (fr)
RU (1)	RU2005133990A (fr)
WO (1)	WO2004089910A1 (fr)
ZA (1)	ZA200508951B (fr)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE10315571A1 (de) *	2003-04-05	2004-10-14	Merck Patent Gmbh	Pyrazolverbindungen
DE10315569A1 (de) *	2003-04-05	2004-10-14	Merck Patent Gmbh	Substituierte Pyrazolverbindungen
DE10315572A1 (de) *	2003-04-05	2004-10-14	Merck Patent Gmbh	Substituierte Pyrazole
EP1805142A4 (fr)	2004-09-23	2009-06-10	Reddy Us Therapeutics Inc	Composes a base de pyridine, leur procede de preparation et compositions les contenant
US7728009B1 (en) *	2005-02-18	2010-06-01	Neurogen Corporation	Thiazole amides, imidazole amides and related analogues
SG162803A1 (en) *	2005-06-27	2010-07-29	Exelixis Inc	Imidazole based lxr modulators
KR101363278B1 (ko)	2005-06-27	2014-02-21	엑셀리시스 페이턴트 컴퍼니 엘엘씨	이미다졸계 ｌｘｒ 변조제
BRPI0614262A2 (pt)	2005-08-02	2011-03-15	Lexicon Pharmaceuticals Inc	aril piridinas e métodos para uso das mesmas
JP2008169191A (ja) *	2006-02-20	2008-07-24	Eisai R & D Management Co Ltd	運動ニューロン疾患治療剤
EP2121621B1 (fr)	2006-12-08	2014-05-07	Exelixis Patent Company LLC	Modulateurs lxr et fxr
US8524909B2 (en) *	2010-02-02	2013-09-03	Hoffmann-La Roche Inc.	Tetrahydro-pyran derivatives
TW201321367A (zh) *	2011-10-25	2013-06-01	Du Pont	經１，３－二芳基取代之雜環殺蟲劑
EP2850074A1 (fr)	2012-05-16	2015-03-25	E. I. Du Pont de Nemours and Company	Pesticides hétérocycliques substitués par un 1,3-diaryle
GB201312800D0 (en)	2013-07-17	2013-08-28	Heptares Therapeutics Ltd	mGlu5 modulators
WO2015022293A2 (fr) *	2013-08-12	2015-02-19	Basf Se	Composés de pyrazole substitués par 1,3-(hétéro)aryle
TW201601632A (zh)	2013-11-20	2016-01-16	杜邦股份有限公司	１－芳基－３－烷基吡唑殺蟲劑
CR20200464A (es)	2018-03-08	2021-04-14	Incyte Corp	Compuestos diólicos de aminopirazina como inhibidores de pi3k-y
WO2020010003A1 (fr)	2018-07-02	2020-01-09	Incyte Corporation	DÉRIVÉS D'AMINOPYRAZINE UTILISÉS EN TANT QU'INHIBITEURS DE PI3K-γ
AU2019387370A1 (en)	2018-11-30	2021-06-10	Nuvation Bio Inc.	Pyrrole and pyrazole compounds and methods of use thereof

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4146721A (en) *	1969-09-12	1979-03-27	Byk Gulden Lomberg Chemische Fabrik Gmbh	Pyrazol-4-acetic acid compounds
CH518155A (de) *	1970-08-18	1972-01-31	Schaerer Willy	Verfahren zur Erleichterung des Schleifens schraubenlinienförmiger Nuten, bei einer Serie von unter sich gleichen Werkstücken mit je mindestens einer schraubenlinienförmig eingefrästen Nut und Simuliergerät zur Durchführung des Verfahrens
BE793955A (fr)	1972-01-15	1973-07-12	Merck Patent Gmbh	Arylpiperazines et leur procede de preparation
DE2906252A1 (de)	1979-02-19	1980-08-28	Merck Patent Gmbh	Pyrazolderivate, diese enthaltende pharmazeutische zubereitungen und verfahren zu ihrer herstellung
US4631343A (en)	1983-11-07	1986-12-23	Eli Lilly And Company	Cyanopyrazole intermediates
ES2206571T3 (es)	1995-04-20	2004-05-16	G.D. SEARLE & CO.	Agentes de amidino ciclico utiles como inhibidores de la oxido nitrico sintasa.
CA2278307A1 (fr)	1997-01-21	1998-07-23	Siegfried Benjamin Christensen Iv	Nouveaux modulateurs de recepteurs de cannabinoides
US6150393A (en) *	1998-12-18	2000-11-21	Arena Pharmaceuticals, Inc.	Small molecule modulators of non-endogenous, constitutively activated human serotonin receptors
US20010044445A1 (en)	1999-04-08	2001-11-22	Bamaung Nwe Y.	Azole inhibitors of cytokine production
US6632815B2 (en)	1999-09-17	2003-10-14	Millennium Pharmaceuticals, Inc.	Inhibitors of factor Xa
US6407238B1 (en)	1999-10-29	2002-06-18	Boehringer Ingelheim Pharmaceuticals, Inc.	Process of making substituted pyrazoles
WO2001032627A1 (fr)	1999-10-29	2001-05-10	Boehringer Ingelheim Pharmaceuticals, Inc.	Procede de production de pyrazoles substitues
ES2234683T3 (es)	1999-11-05	2005-07-01	Smithkline Beecham Plc	Derivados de isoquinolina y quinazolina con actividad combinada sobre los receptores 5ht1a, 5ht1b y 5ht1d.
EP1395257A1 (fr)	2001-06-12	2004-03-10	Elan Pharmaceuticals, Inc.	Macrocycles utiles dans le traitement de la maladie d'alzheimer
DE10149370A1 (de)	2001-10-06	2003-04-10	Merck Patent Gmbh	Pyrazolderivate
BR0309259A (pt)	2002-04-18	2005-02-09	Pharmacia Corp	Terapia combinada para o tratamento de doença de parkinson com inibidores de ciclooxigenase-2 (cox 2)
WO2003099793A1 (fr) *	2002-05-24	2003-12-04	Takeda Pharmaceutical Company Limited	Derives 1,2-azole presentant une activite hypoglycemique et hypolipidemique
WO2004024705A1 (fr) *	2002-09-10	2004-03-25	Takeda Pharmaceutical Company Limited	Composes heterocycliques a cinq elements
AU2003287965A1 (en) *	2002-10-24	2004-05-13	Carex Sa	Modulation of peroxisome proliferator activated receptors activity
DE10315571A1 (de)	2003-04-05	2004-10-14	Merck Patent Gmbh	Pyrazolverbindungen
DE10315572A1 (de)	2003-04-05	2004-10-14	Merck Patent Gmbh	Substituierte Pyrazole
DE10315569A1 (de)	2003-04-05	2004-10-14	Merck Patent Gmbh	Substituierte Pyrazolverbindungen
US20070093492A1 (en)	2004-03-09	2007-04-26	Weir-Torn Jiaang	Pyrrolidine derivatives

2003
- 2003-04-05 DE DE2003115573 patent/DE10315573A1/de not_active Withdrawn
2004
- 2004-03-08 AT AT04718264T patent/ATE478052T1/de active
- 2004-03-08 AU AU2004228121A patent/AU2004228121B2/en not_active Ceased
- 2004-03-08 RU RU2005133990/04A patent/RU2005133990A/ru not_active Application Discontinuation
- 2004-03-08 CN CNA2004800086295A patent/CN1768043A/zh active Pending
- 2004-03-08 BR BRPI0409002-0A patent/BRPI0409002A/pt not_active Application Discontinuation
- 2004-03-08 JP JP2006504585A patent/JP4740116B2/ja not_active Expired - Fee Related
- 2004-03-08 WO PCT/EP2004/002354 patent/WO2004089910A1/fr not_active Ceased
- 2004-03-08 US US10/551,998 patent/US7566709B2/en not_active Expired - Fee Related
- 2004-03-08 DE DE502004011551T patent/DE502004011551D1/de not_active Expired - Lifetime
- 2004-03-08 MX MXPA05010646A patent/MXPA05010646A/es unknown
- 2004-03-08 KR KR1020057018898A patent/KR20050119194A/ko not_active Withdrawn
- 2004-03-08 ES ES04718264T patent/ES2349922T3/es not_active Expired - Lifetime
- 2004-03-08 EP EP04718264A patent/EP1611107B1/fr not_active Expired - Lifetime
- 2004-03-08 CA CA002521202A patent/CA2521202A1/fr not_active Abandoned
- 2004-04-02 AR ARP040101120A patent/AR043838A1/es unknown
2005
- 2005-11-04 ZA ZA200508951A patent/ZA200508951B/en unknown

Also Published As

Publication number	Publication date
DE10315573A1 (de)	2004-10-14
US20070105871A1 (en)	2007-05-10
ZA200508951B (en)	2007-03-28
AU2004228121B2 (en)	2010-11-04
WO2004089910A1 (fr)	2004-10-21
EP1611107A1 (fr)	2006-01-04
JP2006522036A (ja)	2006-09-28
MXPA05010646A (es)	2005-12-12
ES2349922T3 (es)	2011-01-13
BRPI0409002A (pt)	2006-03-28
US7566709B2 (en)	2009-07-28
CN1768043A (zh)	2006-05-03
AU2004228121A1 (en)	2004-10-21
DE502004011551D1 (de)	2010-09-30
EP1611107B1 (fr)	2010-08-18
RU2005133990A (ru)	2006-03-20
JP4740116B2 (ja)	2011-08-03
KR20050119194A (ko)	2005-12-20
ATE478052T1 (de)	2010-09-15
AR043838A1 (es)	2005-08-17

Legal Events

Date	Code	Title	Description
2009-03-05	EEER	Examination request
2013-05-01	FZDE	Discontinued	Effective date: 20130306

Publication	Publication Date	Title
JP4740115B2 (ja)	2011-08-03	置換ピラゾール
AU2004228121B2 (en)	2010-11-04	1,3,4-substituted pyrazoles for use as 5-HT receptor antagonists in the treatment of psychoses and neurological disorders
JP4795889B2 (ja)	2011-10-19	ベンゾフラン化合物
SK282708B6 (sk)	2002-11-06	Derivát piperazínu so selektivitou pre D-4 receptor, spôsob jeho prípravy, jeho použitie a farmaceutický prostriedok, ktorý ho obsahuje
JP2004502760A (ja)	2004-01-29	ピラゾール誘導体
WO1998041519A1 (fr)	1998-09-24	Nouveaux agonistes de recepteurs de cannabinoides
JP2011153144A (ja)	2011-08-11	置換ピラゾール化合物
JPH054391B2 (fr)	1993-01-19
CA2521199A1 (fr)	2004-10-21	Composes pyrazole
JPH09501171A (ja)	1997-02-04	５ｈｔ１ｄ受容体アンタゴニストとしてのアミド誘導体
JP2002521377A (ja)	2002-07-16	ビフェニル誘導体